Effects on the immune system and toxicity of carboplatin/paclitaxel combination chemotherapy in patients with stage III-IV ovarian and non small cell lung cancer and its role in survival and toxicity.

PURPOSE: To examine the impact of paclitaxel and carboplatin combination chemotherapy on the parameters of the immune system in patients with non small cell lung cancer (NSCLC) and with ovarian cancer before, during and after chemotherapy, and the effect of this combination on the overall patient survival. METHODS: 24 patients with NSCLC and 20 with ovarian cancer (all in stage IIIb-IV) treated with 6 courses of paclitaxel and carboplatin combination chemotherapy were separated into two groups according to their survival group A: long survival (> 12 months for NSCLC; > 30 months for ovarian cancer) group B: short survival (<12 months for NSCLC; <30 months for ovarian cancer). At the same time we studied some immunological parameters (CD3, CD4, CD8, CD56, CD34, IL-3, IFN-γ) in relation with the induced toxicity during chemotherapy. The results were analysed using the ANOVA method. RESULTS: We observed a statistically significant difference of CD4 and CD4/CD8 after chemotherapy between groups A and B (p<0.001 and p< 0.006 respectively), implying that the further increase of T-helper cells after chemotherapy had a positive impact on survival. In addition, statistically interesting was the difference in values of IFN-γ between patients of groups A and B before and after chemotherapy (p< 0.039 and p< 0.027, respectively). Patients with high IL-3 had little chance of toxicity. CONCLUSION: Our findings support that with carboplatin/ paclitaxel combination chemotherapy, important parameters of the immune system (IFN-γ, CD4, CD4/CD8) can be used as prognostic factors for survival, while others (IL-3) as indicators of toxicity.

Pregnancy associated breast cancer: a case report.

Despite its infrequency, pregnancy associated breast cancer implies multiple therapeutic dilemmas. Our patient, a 32-year-old Caucasian, gravida 2, para 2, was diagnosed with cancer of the left breast in the 19th week of gestation. Shortly after she underwent quadrantectomy plus axillary lymph node dissection. Chemotherapy was initiated in the 22(+6) week--four cycles of a combination of endoxan, farmorubicin, and fluorouracil. The patient gave birth in the 35(+6) week to a healthy baby with no apparent malformations. During puerperium she received two more cycles of chemotherapy. She is currently undergoing radiotherapy with tangential fields. Although it is too early to draw conclusions, the malignancy seems to be inactive.

A phase II study with vinorelbine, gemcitabine and cisplatin in the treatment of patients with stage IIIb-IV non-small cell lung cancer (NSCLC).

In our phase II study an acceptable and effective agent like cisplatin was used in combination with vinorelbine and gemcitabine in patients with non-small cell lung cancer (NSCLC). These two new cytostatic drugs have demonstrated, when used as a single-agent treatment, effective response rates (vinorelbine) and minimum toxicity (gemcitabine). The following schedule was used: (i) vinorelbine 25 mg/m2 on days 1 and 8; (ii) gemcitabine 1000 mg/m2 on days 1 and 8; and (iii) cisplatin 75 mg/m2 on day 8. The schedule was repeated every 21 days, with a maximum of six cycles per patient. A total of 31 patients with a mean Karnofsky performance status of 90% were evaluated and 29 of them were finally eligible. Of the patients, five (16.1%) were at stage IIIb and the remainder (83.9%) were at stage IV. The overall response rate was 65% (20 patients); six patients (19.4%) had complete response (CR) and 14 (45.2%) had partial response (PR). Two patients (6.5%) had stable disease and seven (22.6%) had progressive disease. The most notable toxicity was hematologic. Leukoneutropenia was mainly revealed after the third or fourth cycle and granulocyte-colony stimulating factor (G-CSF) was administered in 24 patients (77.4%). Mild anemia was found in almost all patients after the third or fourth cycle (Hb 10-11 g/dl) and eight patients (25.8%) required erythropoietin (EPO). Thrombocytopenia was more often observed compared with other known chemotherapeutic regimens; six patients (19.4%) had grade I thrombocytopenia and therapy was delayed in another four patients (12.9%) due to this complication. Non-hematologic toxicity was mild and well tolerated and consisted of alopecia (54.8%), nausea and vomiting (12.9%), constipation (12.9%), peripheral neuropathy (9.6%), diarrhea (6.5%), stomatitis (3.2%) and local phlebitis (3.2%). The examined combination provides us with one of the best overall responses rates reported, however at the cost of remarkable hematologic toxicity. Therefore, it would be better applied in patients with good performance status. The high response rates give us hope of using this combination as a neoadjuvant regimen.

Non-invasive estimation of pulmonary arterial hypertension in chronic obstructive pulmonary disease.

The feasibility and reliability of the combination of several noninvasive methods using a multivariate method of analysis to predict pulmonary artery hypertension (PAH) is evaluated in 20 patients with chronic obstructive pulmonary disease. These methods comprised arterial blood gases (Pao2, Paco2), pulmonary functional parameters (FEV1), echo-Doppler parameters (tricuspid regurgitation jets, acceleration time on pulmonary valve), computed tomography measurements (transhilar distance, hilar thoracic index, and measurement of the descending branch of the right pulmonary artery to the lower lobe). A multiple stepwise regression analysis (including one Doppler parameter, two parameters of arterial blood gases, and one functional parameter) revealed a coefficient of determination (R2) equal to 0.954 for mean pulmonary artery pressure (MPAP) with a standard error of estimate (S.E.E.) of 5.25 mmHg. A stepwise regression analysis including computed tomography and radiographic parameters revealed an R2 equal to 0.970 for PAP with a S.E.E. of 4.26 mmHg. Logistical regression analysis classified correctly 80% of patients with PAH using noninvasive methods such as the diameter of the main pulmonary artery and the diameter of the left pulmonary arterial branch calculated by computed tomography. Not only the presence of PAH but also the level of MPAP can be estimated by the combination of multiple stepwise and logistical regression analyses.

Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial.

BACKGROUND: The aim of the current prospective, randomized control study was to investigate the effect of dietary omega-3 polyunsaturated fatty acids plus vitamin E on the immune status and survival of well-nourished and malnourished patients with generalized malignancy. METHODS: Sixty patients with generalized solid tumors were randomized to receive dietary supplementation with either fish oil (18 g of omega-3 polyunsaturated fatty acids, PUFA) or placebo daily until death. Each group included 15 well-nourished and 15 malnourished patients. The authors measured total T cells, T-helper cells, T-suppressor cells, natural killer cells, and the synthesis of interleukin-1, interleukin-6, and tumor necrosis factor by peripheral blood mononuclear cells before and on Day 40 of fish oil supplementation. Karnofsky performance status, nutritional state, and survival were also estimated. RESULTS: The ratio of T-helper cells to T-suppressor cells was significantly lower in malnourished patients. Omega-3 PUFA had a considerable immunomodulating effect by increasing this ratio in the subgroup of malnourished patients. There were no significant differences in cytokine production among the various groups, except for a decrease in tumor necrosis factor production in malnourished cancer patients, which was restored by omega-3 fatty acids. The mean survival was significantly higher for the subgroup of well-nourished patients in both groups, whereas omega-3 fatty acids prolonged the survival of all the patients. CONCLUSIONS: Malnutrition appears to be an important predictor of survival for patients with end stage malignant disease. Omega-3 polyunsaturated fatty acids had a significant immunomodulating effect and seemed to prolong the survival of malnourished patients with generalized malignancy.

Treatment of penile intraepithelial neoplasia (PIN) with interferon alpha-2a, CO2 laser (vaporization) and 5-fluorouracil 5% (5-FU).

This study was undertaken to assess the effectiveness of CO2 laser (vaporization), 5-FU topical application and Interferon (IFN alpha-2a) parenterally in the therapy of penile intraepithelial neoplasia (PIN). From March 1986 to September 1991, 1,372 men, sexual partners of women with condylomata accuminata or flat or cervical intraepithelial neoplasia (CIN), were submitted to peoscopy, of 1,019 men who presented with various lesions caused by human papillomavirus (HPV)-confirmed histologically-208 were treated for PIN. The best treatment modalities irrespective of grade of lesion were found to be the combination of 5-FU plus CO2 laser vaporisation plus IFN alpha-2a (high dose) (96.15%), the combination of 5-FU plus CO2 laser vaporization (87.09%) and the combination of CO2 laser vaporization plus IFN alpha-2a (high dose) (80%). It is concluded that IFN alpha-2a (low dose) can be used as first line treatment in combination with 5-FU in patients with PIN II and as an adjuvant treatment (high dose) in patients with recurrent PIN I and PIN III.

Advanced non-small cell lung cancer chemotherapy: a randomized trial of two active regimens (MVP and PE).

The treatment of advanced or metastatic NSCLC remains a controversial issue and cisplatin-based combination chemotherapy is by far the most common treatment. Two of these cisplatin-based standard combinations, MVP and PE, were compared in this study in order to evaluate their response rates and survival times. Eighty-five previously untreated NSCLC patients were randomly selected to receive either MVP or PE and 72 of these patients were eligible for evaluation for response rate and survival. Response rates for MVP were: CR 11%, PR 35%, SD 19% and PD 35% and for PE: CR 0%, PR 26%, SD 22% and PD 52%. The median survival time was 9.7 months for MVP and 6.9 months for PE. Both schedules were well tolerated. The administration of MVP in advanced NSCLC resulted in superior response rates and survival times over those produced by PE.

Incidence of benign and malignant breast disorders in women taking hormones (contraceptive pill or hormonal replacement therapy).

The incidence of breast disorders, in a series of 142 women of reproductive age who received combined oral contraception (OC) for birth control and in 98 postmenopausal women who received hormone replacement therapy (HRT) with estrogens and progestins, for seven years, was compared with control groups. A lower incidence of benign breast diseases was observed among OC users (p < 0.001) and HRT recipients (p < 0.001). No differences were observed in the incidence of breast cancer among the groups studied. OC use and HRT do not increase the risk for breast cancer and decrease the incidence of benign breast diseases.

PIP: To assess the association between benign and malignant breast disease and hormone use, the incidence of such disorders was compared in 142 women (mean age, 29.9 years) who took combined oral contraceptives (OCs) for birth control and 98 postmenopausal women (mean age, 59.4 years) receiving hormone replacement therapy (HRT). The duration of use in both groups was 7 years. Women with a family history of breast cancer were excluded. Controls for OC users included 975 recruited from a family planning clinic; 323 women attending a menopause clinic served as controls for the HRT group. Participants received both mammography and/or breast ultrasound at baseline and at regular age-appropriate intervals. A statistically significant (p 0.001) difference between hormone users and controls was observed in the incidence of benign breast disease. There were 45 cases (31.69%) of benign breast disease among OC users compared with 536 (54.97%) among their controls and 19 such cases (19.88%) among HRT users compared with 121 (37.46%) among their controls. There was no observed breast cancer among women in either the OC or HRT group. These findings support the hypothesis that hormonal treatment has a beneficial effect on breast tissue and does not increase the risk of breast cancer.

Sequential chemo-immunotherapy treatment of metastatic malignant melanoma.

Twelve patients with recurring metastatic inoperable malignant melanoma (performance status ECOG 0-1), received the following chemotherapy: tamoxifen p.o., carmustine i.v., dacarbazine i.v., and cisplatin i.v., followed by immunotherapy: interleukin-2 s.c. and interferon-alpha s.c. The treatment cycle was repeated every 6 weeks. Total response rate was 66.6%, with 25% (3 patients) achieving complete cure that has persisted for a period of 17.75 months (mean). In addition, different responses to treatment were observed between the local recurrence lesions and the metastatic lesions. Medium to severe side effects were observed, all but one of them being reversible (neurotoxicity), such as fever, anemia, leukopenia: nephrotoxicity, neurotoxicity, and dyspnea.

The effect of dietary omega-3 polyunsaturated fatty acids on T-lymphocyte subsets of patients with solid tumors.

The effect of omega-3 polyunsaturated fatty acids (PUFA) on the immune system seems to be beneficial. There has been a number of studies concerning the effect of dietary omega-3 PUFA on different immune parameters. The aim of our present study was to investigate the effect of dietary omega-3 PUFA on T-cell subsets and natural killer (NK) cells of patients with solid tumors. We studied 20 patients with solid tumors who received 18 g fish oil/day for 40 consecutive days. We detected a significant increase in T-helper/T-suppressor cell ratio 40 days into omega-3 supplementation, due mainly to a decrease in the number of suppressor T cells. We concluded that dietary omega-3 fatty acids may have a beneficial effect on the already compromised immune system of patients suffering from solid tumors.